Neuroscience letters
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Neuroscience letters · Nov 2014
Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia.
Global cerebral ischemia (GCI) causes energy deficiency results in excessive release of glutamate from neurons. Astrocytic glutamate transporters play a predominant role in keeping extracellular glutamate concentrations below excitotoxic levels. Glutamate transporter 1 (GLT-1) may account for more than 90% of glutamate uptake in adult forebrain. ⋯ Our results showed that post-GCI administration of Harmine could attenuate cerebral infarct volume and decrease neurons death. It also caused significantly elevation of GLT-1 mRNA and protein and remarkably attenuation of astrocyte activation. We provide novel clues in understanding the mechanisms of which Harmine exerts its neuroprotective activity in neurological disorders.
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Neuroscience letters · Nov 2014
The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn.
The purpose of this study was to validate the effects of tianeptine on serotonergic and noradrenergic neurotransmission in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of intrathecally administered tianeptine on mechanical allodynia were assessed. ⋯ Intrathecal tianeptine significantly increased the paw withdrawal thresholds in a dose-dependent manner and the antiallodynic effect was antagonized by dihydroergocristine and yohimbine. Microdialysis studies revealed that tianeptine increased the levels of 5-HT and NE in the spinal dorsal horn. These findings suggest that tianeptine may be effective for the management of neuropathic pain and that its analgesic mechanism is exerted by increased levels of 5-HT and NE in the synaptic cleft at the spinal level.
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Neuroscience letters · Nov 2014
Piezo2 channel conductance and localization domains in Merkel cells of rat whisker hair follicles.
We have recently shown that Merkel cells transduce tactile stimuli via Piezo2 channels to initiate the sense of touch. Here we performed patch-clamp recordings to assess single channel activity on the membranes of Merkel cells in whisker hair follicles. Under the cell-attached configuration, most Merkel cell membrane patches showed large outward unitary currents with single channel conductance being ∼200pS. ⋯ While the MA current decayed rapidly, a small steady-state current component with significant channel noise could be observed. Applications of stationary and non-stationary fluctuation analyses to the MA currents yielded single channel conductance of 32.5±3.8 and 54.0±5.3pS, respectively. The lack of mechanical responses under the cell-attached configuration and the existence of Piezo2 MA currents under the whole-cell configuration raised a possibility that Piezo2 channels are preferentially located on Merkel cell processes, the membrane domains inaccessible by recording electrodes.
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Neuroscience letters · Nov 2014
Nociceptive sensitization and BDNF up-regulation in a rat model of traumatic brain injury.
Chronic pain after traumatic brain injury (TBI) is very common, but the mechanisms linking TBI to pain experienced in the periphery have not been described. In this set of studies we examined nociceptive sensitization and changes in spinal cord gene expression using the rat lateral fluid percussion model of mild TBI. ⋯ We also found that spinal cord levels of brain derived neurotrophic factor (BDNF) but not several other pain-related genes were up-regulated one week after injury. Our findings suggest that TBI-induced up-regulation of spinal BDNF levels might contribute to chronic TBI-related pain, and that the lateral fluid percussion model might be useful for exploring this relationship.
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DTNBP1 is a key candidate gene associated with schizophrenia. The expression of its protein product, dysbindin-1, is altered in the brains of schizophrenic patients; however, the physiological functions of dysbindin-1 in the central nervous system are unclear. Several studies have shown that both dysbindin-1 and histone deacetylase 3 (HDAC3) can be phosphorylated by the DNA-dependent protein kinase complex. ⋯ The interaction between dysbindin-1 and HDAC3 occurred in an isoform-specific manner: HDAC3 coupled with dysbindin-1A and -1B, but not -1C. We also found that dysbindin-1B expression was increased in the nucleus in the presence of HDAC3, and, conversely, that the phosphorylation level of HDAC3 increased in the presence of dysbindin-1B. Taken together, these results identify a novel binding partner for dysbindin-1, which may potentially provide a new avenue for research into the neurological mechanisms of schizophrenia.